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Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth
Evidence suggests that n-3 polyunsaturated fatty acids may act as activators of the Nrf2 antioxidant pathway. The antioxidant response, in turn, promotes neuronal differentiation and neurite outgrowth. Nrf2 has recently been suggested to be a cell intrinsic mediator of docosohexanoic acid (DHA) sign...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101469/ https://www.ncbi.nlm.nih.gov/pubmed/33502893 http://dx.doi.org/10.1091/mbc.E20-09-0599 |
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author | Drolet, Jennifer Buchner-Duby, Brodie Stykel, Morgan G. Coackley, Carla Kang, Jing X. Ma, David W. L. Ryan, Scott D. |
author_facet | Drolet, Jennifer Buchner-Duby, Brodie Stykel, Morgan G. Coackley, Carla Kang, Jing X. Ma, David W. L. Ryan, Scott D. |
author_sort | Drolet, Jennifer |
collection | PubMed |
description | Evidence suggests that n-3 polyunsaturated fatty acids may act as activators of the Nrf2 antioxidant pathway. The antioxidant response, in turn, promotes neuronal differentiation and neurite outgrowth. Nrf2 has recently been suggested to be a cell intrinsic mediator of docosohexanoic acid (DHA) signaling. In the current study, we assessed whether DHA-mediated axodendritic development was dependent on activation of the Nrf2 pathway and whether Nrf2 protected from agrochemical-induced neuritic retraction. Expression profiling of the DHA-enriched Fat-1 mouse brain relative to wild type showed a significant enrichment of genes associated with neuronal development and neuronal projection and genes associated with the Nrf2-transcriptional pathway. Moreover, we found that primary cortical neurons treated with DHA showed a dose-dependent increase in Nrf2 transcriptional activity and Nrf2-target gene expression. DHA-mediated activation of Nrf2 promoted neurite outgrowth and inhibited oxidative stress-induced neuritic retraction evoked by exposure to agrochemicals. Finally, we provide evidence that this effect is largely dependent on induction of the Nrf2-target gene NAD(P)H: (quinone acceptor) oxidoreductase 1 (NQO1), and that silencing of either Nrf2 or Nqo1 blocks the effects of DHA on the axodendritic compartment. Collectively, these data support a role for the Nrf2-NQO1 pathway in DHA-mediated axodendritic development and protection from agrochemical exposure. |
format | Online Article Text |
id | pubmed-8101469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81014692021-06-16 Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth Drolet, Jennifer Buchner-Duby, Brodie Stykel, Morgan G. Coackley, Carla Kang, Jing X. Ma, David W. L. Ryan, Scott D. Mol Biol Cell Brief Report Evidence suggests that n-3 polyunsaturated fatty acids may act as activators of the Nrf2 antioxidant pathway. The antioxidant response, in turn, promotes neuronal differentiation and neurite outgrowth. Nrf2 has recently been suggested to be a cell intrinsic mediator of docosohexanoic acid (DHA) signaling. In the current study, we assessed whether DHA-mediated axodendritic development was dependent on activation of the Nrf2 pathway and whether Nrf2 protected from agrochemical-induced neuritic retraction. Expression profiling of the DHA-enriched Fat-1 mouse brain relative to wild type showed a significant enrichment of genes associated with neuronal development and neuronal projection and genes associated with the Nrf2-transcriptional pathway. Moreover, we found that primary cortical neurons treated with DHA showed a dose-dependent increase in Nrf2 transcriptional activity and Nrf2-target gene expression. DHA-mediated activation of Nrf2 promoted neurite outgrowth and inhibited oxidative stress-induced neuritic retraction evoked by exposure to agrochemicals. Finally, we provide evidence that this effect is largely dependent on induction of the Nrf2-target gene NAD(P)H: (quinone acceptor) oxidoreductase 1 (NQO1), and that silencing of either Nrf2 or Nqo1 blocks the effects of DHA on the axodendritic compartment. Collectively, these data support a role for the Nrf2-NQO1 pathway in DHA-mediated axodendritic development and protection from agrochemical exposure. The American Society for Cell Biology 2021-04-01 /pmc/articles/PMC8101469/ /pubmed/33502893 http://dx.doi.org/10.1091/mbc.E20-09-0599 Text en © 2021 Drolet et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Brief Report Drolet, Jennifer Buchner-Duby, Brodie Stykel, Morgan G. Coackley, Carla Kang, Jing X. Ma, David W. L. Ryan, Scott D. Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title | Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title_full | Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title_fullStr | Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title_full_unstemmed | Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title_short | Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth |
title_sort | docosahexanoic acid signals through the nrf2–nqo1 pathway to maintain redox balance and promote neurite outgrowth |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101469/ https://www.ncbi.nlm.nih.gov/pubmed/33502893 http://dx.doi.org/10.1091/mbc.E20-09-0599 |
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